title: Ischemic preconditioning induces autophagy and limits necrosis in human recipients of fatty liver grafts, decreasing the incidence of rejection episodes.
abstract: Whether ischemic preconditioning (IP) reduces ischemia/reperfusion (I/R) injury in human normal and fatty livers remains controversial. We compared two independent groups of liver donor transplants with versus without steatosis to evaluate IP consequences. Liver donors with (n=22) or without (n=28) steatosis either did or did not undergo IP before graft retrieval. Clinical data from the recipients, as well as histological and immunohistological characteristics of post-reperfusion biopsies were analyzed. Incidence of post-reperfusion necrosis was increased (10/10 versus 9/14, respectively; P<0.05) and the clinical outcome of recipients was worse for non-IP steatotic liver grafts compared with non-IP non-steatotic grafts. IP significantly lowered the transaminase values only in patients receiving a non-steatotic liver. An increased expression of beclin-1 and LC3, two pro-autophagic proteins, tended to decrease the incidence of necrosis (P=0.067) in IP steatotic livers compared with non-IP steatotic group. IP decreased the incidence of acute and chronic rejection episodes in steatotic livers (2/12 versus 6/10; P=0.07 and 2/12 versus 7/10; P<0.05, respectively), but not in non-steatotic livers. Thus, IP may induce autophagy in human steatotic liver grafts and reduce rejection in their recipients.
authors.affiliation: AP-HP, Hôpital Paul Brousse, Service de Biochimie et Biologie Moléculaire, 14 Avenue Paul Vaillant Couturier, Villejuif Cedex 94804, France.
authors.forename: D
authors.initials: D
authors.lastname: Degli Esposti
authors.forename: M
authors.initials: M
authors.lastname: Sebagh
authors.forename: P
authors.initials: P
authors.lastname: Pham
authors.forename: M
authors.initials: M
authors.lastname: Reffas
authors.forename: C
authors.initials: C
authors.lastname: Poüs
authors.forename: C
authors.initials: C
authors.lastname: Brenner
authors.forename: D
authors.initials: D
authors.lastname: Azoulay
authors.forename: A
authors.initials: A
authors.lastname: Lemoine
mesh_terms: D000328:Adult; D001343:Autophagy; D005234:Fatty Liver / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery*; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D015994:Incidence; D019194:Ischemic Preconditioning; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D015427:Reperfusion Injury / Q000453:epidemiology* / Q000473:pathology / Q000503:physiopathology; D014019:Tissue Donors